Background: Chronic administration of several irreversible monoamine oxidase (MAO) inhibitors induces a down-regulation of tryptamine and 5-hydroxytryptamine(2) receptors in rat brain, but there is a paucity of information available on the effects of reversible MAO-A inhibitors on these receptors.
Methods: Acute and chronic experiments were conducted in rats and the effects of the irreversible monoamine oxidase inhibitor, phenelzine and the reversible MAO type-A inhibitors, moclobemide and brofaromine, on tryptamine and 5-hydroxytryptamine(2) receptors were analysed using radioligand binding techniques. In addition, activities of MAO-A and -B were determined radiochemically and brain and/or urine levels of tryptamine, 5-hydroxytryptamine, 3-methoxy-4-hydroxyphenylglycol (MHPG), beta-phenylethylamine, brofaromine and moclobemide were determined by chromatographic procedures.
Results: After 30 days of administration, moclobemide and brofaromine selectively inhibited brain MAO-A activity and phenelzine inhibited MAO-A and -B to equal extents. All three drugs caused a significant down-regulation of tryptamine receptors, whereas only phenelzine significantly down-regulated 5-hydroxytryptamine(2) receptors. In a comparison of phenelzine and brofaromine, both caused marked elevations of urinary tryptamine and decreases of urinary MHPG levels, while only phenelzine increased beta-phenylethylamine levels. After 14 days of administration, phenelzine, but not moclobemide or brofaromine, significantly increased levels of tryptamine in brain; all three drugs significantly increased 5-HT levels.
Limitations: 24-h urine samples were not collected for moclobemide-treated animals and brain levels of tryptamine were not measured after 30-day administration.
Conclusions: These studies revealed marked neurochemical differences among phenelzine, moclobemide and brofaromine which could contribute to their actions in the clinical setting.